The pathogenesis of this neovascularization is not fully understood, although the VEGF pathway is well known to be involved in angiogenesis and was implicated in the development of the new vessels under the macula. The VEGFs are the most specific and potent stimulators of the angiogenesis. VEGF-A is a 45kD glycoprotein binding to transmembrane tyrosine kinase receptors, VEGFRs, which activates a cascade of downstream factors. VEGF-A has the strongest pro-angiogenic effect in the retina by promoting proliferation, sprouting and tubing of the endothelial cells. It can bind to at least two receptors -VEGFR1 and VEGFR2, although the most of the proangiogenic activity appears to be mediated through VEGFR2. Expression of a VEGFR2 isoform that lacks both the intracellular signaling domain and the transmembrane domain, represents a soluble form of the receptor, inactivating VEGF extracellularly.